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Principal Investigators

Our laboratory studies all aspects of skeletal biology. The skeleton is made of two tissues, cartilage and bone and three main cell types chondrocyte in cartilage, osteoblast, and osteoclast in bone. Chondrocyte and osteoblast are of mesenchymal origin whereas osteoclasts derive from the myelomonocytic lineage.

In terms of developmental biology, we have identified transcription factors (“master genes”) that control positively or negatively the entire cascade of differentiation of mesenchymal cells into osteoblasts. We have expanded this work to chondrocyte as well as to differentiation of cells of the parathyroid gland, an endocrine gland that plays a major role during bone remodeling. We have also identified microRNAs that modulate the activity of Runx2, the master transcription factor of osteoblast differentiation.

In terms of physiology which is currently the main interest of the lab, we have pursued two distinct questions. The first one is to provide a molecular genetics explanation for known functions of the skeleton, the regulation of which was poorly understood. In doing so, we have, for instance, provided a genetic explanation for why mineralization of the extracellular matrix occurs only in bone, as well as for pathological calcification. We have also shown that bone mass accrual is under the control of the brain and provided a road map of the endocrine and neuronal circuitry implicated in the central regulation of bone mass.

More recently our laboratory has asked another question: Does the skeleton have any other functions than making bone? In addressing this question we have identified osteocalcin as a bone-derived hormone that is necessary and sufficient to promote multiple physiological functions that are all characterized by the fact they decline early in life and are needed for survival in a hostile environment. Those include but are not limited to male fertility, memory, adaptation to exercise, energy expenditure, insulin secretion and glucose homeostasis and aspects of the stress response. Our goals are to decipher the molecular bases of these functions and to demonstrate that the endocrine function of bone, explains why many physiological functions are regulated differently in bony vertebrates than in other animals. To address these challenges we use mouse genetics, molecular and cellular biology approaches as well as physiological assays. Current projects in the lab include:

Unraveling the molecular bases of bone metastasis from prostate cancer.

Defining the role of osteocalcin in energy metabolism.

Defining the role of osteocalcin in the central and peripheral nervous system.

Demonstrating the implication of the dysregulation of osteocalcin in the pathogenesis of human diseases.